Germline mutation landscape of DNA damage repair genes in African Americans with prostate cancer highlights potentially targetable RAD genes

Indu Kohaar (), Xijun Zhang, Shyh-Han Tan, Darryl Nousome, Kevin Babcock, Lakshmi Ravindranath, Gauthaman Sukumar, Elisa Mcgrath-Martinez, John Rosenberger, Camille Alba, Amina Ali, Denise Young, Yongmei Chen, Jennifer Cullen, Inger L. Rosner, Isabell A. Sesterhenn, Albert Dobi, Gregory Chesnut, Clesson Turner, Clifton Dalgard, Matthew D. Wilkerson, Harvey B. Pollard, Shiv Srivastava and Gyorgy Petrovics ()
Additional contact information
Indu Kohaar: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Xijun Zhang: Uniformed Services University of the Health Sciences
Shyh-Han Tan: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Darryl Nousome: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Kevin Babcock: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Lakshmi Ravindranath: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Gauthaman Sukumar: Uniformed Services University of the Health Sciences
Elisa Mcgrath-Martinez: Uniformed Services University of the Health Sciences
John Rosenberger: Uniformed Services University of the Health Sciences
Camille Alba: Uniformed Services University of the Health Sciences
Amina Ali: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Denise Young: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Yongmei Chen: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Jennifer Cullen: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Inger L. Rosner: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Isabell A. Sesterhenn: Joint Pathology Center
Albert Dobi: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Gregory Chesnut: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Clesson Turner: Uniformed Services University of the Health Sciences
Clifton Dalgard: Uniformed Services University of the Health Sciences
Matthew D. Wilkerson: Uniformed Services University of the Health Sciences
Harvey B. Pollard: Uniformed Services University of the Health Sciences
Shiv Srivastava: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
Gyorgy Petrovics: Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract In prostate cancer, emerging data highlight the role of DNA damage repair genes (DDRGs) in aggressive forms of the disease. However, DDRG mutations in African American men are not yet fully defined. Here, we profile germline mutations in all known DDRGs (N = 276) using whole genome sequences from blood DNA of a matched cohort of patients with primary prostate cancer comprising of 300 African American and 300 European Ancestry prostate cancer patients, to determine whether the mutation status can enhance patient stratification for specific targeted therapies. Here, we show that only 13 of the 46 DDRGs identified with pathogenic/likely pathogenic mutations are present in both African American and European ancestry patients. Importantly, RAD family genes (RAD51, RAD54L, RAD54B), which are potentially targetable, as well as PMS2 and BRCA1, are among the most frequently mutated DDRGs in African American, but not in European Ancestry patients.

Date: 2022
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DOI: 10.1038/s41467-022-28945-x

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